1. Field of the Invention
The present invention relates to a method of manufacturing a microneedle.
2. Description of the Related Art
Percutaneous absorption has been known as one of the methods for administering a drug by permitting it to permeate through the skin. In this method, a liquid or gel of the drug is applied on the surface of a living body such as the skin or mucous membrane.
This method is noninvasive, and makes it possible to simply administer the drug without giving pain to the human body. However, the applied drug is liable to be removed by perspiration or external contact. Another problem may arise in terms of safety since skin failure occurs by long-term administration. In addition, the drug is hardly absorbed in the body merely by applying it on the surface of the body when the drug to be administered has a high molecular weight or the drug is water soluble, and percutaneous absorption of such drug is difficult.
Accordingly, a noticed method is to directly inject the drug beneath the skin by perforating the skin using a microneedle array having many needles of micron order in order to permit the drug to be efficiently absorbed into the body. This method enables simple subcutaneous administration without using any special devices (see U.S. Pat. No. 6,183,434).
The microneedle used in this method is required to have sufficient fineness and point angle for perforating the skin, and a sufficient length for permitting the drug solution to be permeated under the skin. Consequently, it is thought to be desirable that the needle diameter is from several μm to 100 μm, and the needle length is selected so that the needle penetrates through corneum that is an outermost layer of the skin while the needle does not reach a nerve layer, or specifically from scores of μm to hundreds of μm. The material constituting the needle is required to be harmless to the human body even when the needle is broken and left behind in the body. Materials considered to be promising include medical use silicone resins and biocompatible resins such as maltose, polylactate and dextran resins (see Jpn. Pat. Appln. KOKAI Publication No. 2005-21677).
For mass production of needles having such a fine structure with a low production cost, transcription molding methods represented by injection molding method, imprint method and casting method are effective. However, a mold having inversed projections and recesses of a desired shape is necessary for molding by any of the above-mentioned methods, and a quite complicated production process is required for forming a structure that is necessary to have a high aspect ratio (a ratio of the height or depth to the diameter of the structure) and an acute tip as the microneedle.
In a proposed method of manufacturing the microneedle, the tip of the needle is sharpened by anisotropic wet etching of a single crystal material such as a silicon wafer by taking advantage of a difference in etching rates between respective crystal orientations of the singe crystal. However, a strict control of the anisotropic wet etching time is necessary for sharpening the tip of the needle, and a high degree of processing technology becomes necessary (Jpn. Pat. Appln. KOKAI Publication No. 2002-79499).
Other proposed methods include controlling the point angle of the needle by changing the light exposure value while an exposure mask is moved (see Jpn. Pat. Appln. KOKAI Publication No. 2005-246595), or combining wet etching using a chemical solution and plasma etching (see Jpn. Pat. Appln. KOKAI Publication No. 2002-239014).
Another method of manufacturing microneedles to form a microneedle patch includes the steps of forming tips of the microneedles by isotropic etching under a resist mask, and forming microneedles with a desired height by anisotropic etching (see Jpn. Pat. Appln. KOKAI Publication No. 2005-199392).
However, the above-mentioned manufacturing methods involve a problem in the cost and time since the methods include many complicated steps of forming a thermal oxide layer, applying a resist, forming a mask pattern by photolithography, applying isotropic etching, applying anisotropic etching, removing a sidewall deposit layer, and applying gradient etching.
While the microneedle is required to be uniformly formed particularly with respect to the height since the microneedle should reliably arrive at body tissues such as the epidermis, it is difficult to form the microneedle with high accuracy by the above-mentioned methods.
A special exposure apparatus that is not usually used, a high precision machining technique and a complicated manufacturing process are often needed for satisfying the structural requirement of the microneedle, since a high aspect ratio as well as sharpening the tip are necessary in the conventional methods for manufacturing the microneedle. It is another problem that stripped pieces of the mask contaminate around the mask as etching advances.